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Pharmacology: Pharmacodynamics: Dextromethorphan HBr: Dextromethorphan is a methylated dextroisomer of Codeine analog, Levorphanol. Unlike Levorphanol, however, it has no significant analgesic properties and does not depress respiration or predispose to addiction.
Dextromethorphan acts centrally by depressing the cough center in the medulla of the brain and therefore elevates the threshold for coughing. Its antitussive potency is nearly equal to that of Codeine.
Phenylephrine HCl: Phenylephrine is a powerful vasoconstrictor. It is used as a nasal decongestant and cardiotonic agent. Phenylephrine is a postsynaptic α1-receptor agonist with little effect on β-receptors of the heart. Parenteral administration of phenylephrine causes a rise in systolic and diastolic pressures, a slight decrease in cardiac output, and a considerable increase in peripheral resistance; most vascular beds are constricted, and renal, splanchnic, cutaneous, and limb blood flows are reduced while coronary blood flow is increased. Phenylephrine also causes pulmonary vessel constriction and subsequent increase in pulmonary arterial pressure. Vasoconstriction in the mucosa of the respiratory tract leads to decreased edema and increased drainage of sinus cavities.
Paracetamol: Paracetamol exhibits analgesic and antipyretic activity by inhibiting prostaglandin synthesis. It produces analgesia by elevating the pain threshold and antipyresis through its action on the hypothalamic heat regulating center.
In therapeutic doses, the analgesic and antipyretic actions of Paracetamol are comparable to that of aspirin. Paracetamol does not adversely affect platelet function and hemostasis.
Pharmacokinetics: Dextromethorphan HBr: Dextromethorphan is rapidly absorbed from the gastrointestinal tract and exerts its effect within 15 to 30 minutes after oral administration. The duration of action is approximately 3 to 6 hours with conventional dosage forms.
Dextromethorphan is metabolized in the liver and excreted as unchanged dextromethorphan and demethylated morphinan compounds. Up to 56% of dose is excreted in the urine, with about 8% being excreted unchanged in 6 hours.
Phenylephrine HCl: Phenylephrine is completely absorbed after oral administration. It has a reduced bioavailability (compared to pseudoephedrine) following oral administration due to significant first-pass metabolism in the intestinal wall. Compared to IV administration, bioavailability is approximately 38%. Peak serum concentrations are achieved approximately 0.75-2 hours following oral administration.
Phenylephrine undergoes extensive first-pass metabolism in the intestinal wall and extensive metabolism in the liver. Sulfate conjugation, primarily in the intestinal wall, and oxidative metabolism by monoamine oxidase (MAO) represent the principle routes of metabolism. Glucuronidation occurs to a lesser extent. Phenylephrine and its metabolites are mainly excreted in urine.
Paracetamol: Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. After oral administration, peak plasma concentrations of Paracetamol are attained within 10 to 60 minutes, after 8 hours, only small amounts of the drug are detectable in plasma.
Paracetamol is rapidly and uniformly distributed into most body tissues. About 25% of Paracetamol in the blood is bound to plasma proteins.
Paracetamol has plasma half-life of 1.25 to 3 hours which may be prolonged after toxic doses or in patients with liver damage. It is metabolized by microsomal enzyme systems in the liver. About 80 to 85% of Paracetamol in the body undergoes conjugation principally with glucuronic acid to a lesser extent with sulphuric acid. A small amount is conjugated with cystene and also deacylated, probably to p-aminophenol, which can cause methemoglobinemia.
Paracetamol is excreted in urine principally as glucuronide with small amounts of sulfate, mercaptate, and unchanged drug. Approximately 85% of a dose of Paracetamol is excreted in urine as free and conjugated Paracetamol within 24 hours after ingestion.
